The present invention relates to a unique oral care rinse compositions containing a dispersion of certain silicones in certain surfactants. When added to water these dispersions are stable and are distinct from solutions, emulsions and microemulsions. These dispersions are referred to hereinafter as ULTRAMULSION.TM. dispersions. This trademark is the property of Whitehill Oral Technologies, Inc. For further information regarding ULTRAMULSION.TM. dispersions, see copending application Ser. No. 08/144,778, now U.S. Pat. No. 5,538,667, the disclosure of which is hereby incorporated herein by reference. See also copending patent application Ser. Nos. 08/462,613; 08/462,203; 08/462,600; 08/463,010; 08/461,698; 08/464,403; and 08/462,599; all filed on Jun. 5, 1996, the disclosures of which are hereby incorporated by reference.
The ULTRAMULSION.TM. dispersion based oral care rinses of the present invention exhibit unique and unexpected substantivity to oral surfaces including teeth and gums while providing a reservoir for various lipid soluble, essential oil, active ingredients resulting in antiplaque, antibacterial, antigingivitis benefits that last for extended periods. This combination of enhanced substantivity and the reservoir effect described in detail below are further combined with excellent particle size to provide optimum coatings to the oral cavity.
Other oral care products containing the ULTRAMULSION.TM. dispersions of the present invention include: spray, gels, creams, toothpastes, tooth powders, denture cleaning tablets, dental floss, interproximal simulators, mints, and chewing gums. These products are described and claimed in the referenced copending patent applications.
The compositions of the present invention may be used by dentists and hygienists in various professional oral hygiene treatments and/or may be used by consumers in various at-home oral hygiene programs without professional supervision.
As to Antiplaque Benefits:
The present invention further relates to the interference with the formation of plaque. Plaque is a microbial coating on tooth surfaces, bound together by natural polymers (e.g., mucopolysaccharides) formed by microbial action on the cell debris, food remnants, sugars and starches in the mouth. Embedded in this polymer matrix are the bacteria normal to the oral cavity but, when trapped against tooth surfaces and protected by the matrix from easy removal, are in excellent position for "mischief." Most dental texts implicate plaque in the formation of caries, or tooth decay. In addition, these embedded bacteria release toxins that cause gingivitis, bleeding and swelling of the gums. Gingivitis can lead to periodontitis in which gums recede, pockets of infection form and teeth loosen.
Plaque formation is an ongoing process. Various other mouth rinse and mouth pre-rinse preparations make antiplaque, and/or antigingivitis claims. One disadvantage of these preparations is that only a relatively short time during which the teeth are being cleaned or the mouth is being rinsed is available for these preparations to take effect. For example, see the "Transport Kinetics Ethanol and Sorbitol Effects" Listerine.RTM. and Listerine.RTM. Coolmint as discussed below. These preparations generally have little residual effect on plaque formation.
Effective oral hygiene requires that three control elements be maintained by the individual:
1. Physical removal of stains, plaque and tartar.
This is accomplished in the strongest sense by scraping and abrasion in the dentist's office. Self administered procedures are required frequently between visits and range from tooth brushing with an appropriate abrasive toothpaste through flossing and water jet action down to certain abrasive foods and even the action of the tongue against tooth surfaces. PA1 This is required to remove: food debris and staining substances before they adhere to the tooth surfaces; normal dead cellular (epithelial) material which is continually sloughed off from the surfaces of the oral cavity and microbial degradation products derived from all of the above. Besides the obvious hygienic and health benefits related to simple cleanliness provided by surfactants, there is an important cosmetic and sense-of-well-being benefit provided by surfactant cleansing. Research has shown that the primary source of bad breath is the retention and subsequent degradation of dead cellular material sloughed off continuously by the normal, healthy mouth. PA1 This is perhaps the most difficult to provide in today's fast-paced work and social environment. Most people recognize that their teeth should be brushed at least 3 times a day plus after each snacking occasion, and rinsed twice a day. PA1 The simple fact is that most of the population brush once a day, some brush morning and evening, but precious few carry toothbrush and dentifrice to use the other three or four times a day for optimal oral hygiene. Consumer research suggests that the population brushes an average of 1.2 times a day. Thus, the 24 hour period between brushings for a majority of the population provides optimum plaque forming conditions with no interruptions. Less than half of the population rinse once a day. PA1 a. the dispersed silicones, which are insoluble in said surfactant, are oriented by the surfactant such that when dispersed in water they are particularly adept at forming oriented, coatings on surfaces of the mouth with enhanced substantivity, and PA1 b. the particle size of the dispersed silicone is from between about 0.1 and about 10 microns, with a particle size distribution such that from between about 80 and 95% of the dispersed silicone is within this particle size range. These stable dispersions are described as ULTRAMULSION.TM. dispersions, which, together with their physical properties, when contained in oral care rinses, provide these rinses with enhanced substantivity to mouth surfaces, where the non continuous silicone phase functions as a reservoir for various active ingredients contained therein, including but not limited to an essential mixture of thymol, eucalyptol, menthol and methyl salicylate.
2. Surfactant Cleansing.
3. Frequency of Cleansing.
Since plaque is regarded by most of the dental profession as a causative agent leading to various dental pathologies as noted above, there is considerable desire by most consumers to disrupt or prevent the formation of plaque on a daily basis. There are three oral care strategies which address the problem of plaque: abrasion, antimicrobial agents and removal of precursors to plaque.
1. Abrasive removal of the plaque film, once it has firmly adhered to the tooth surface, is the only totally effective cleansing mechanism. Again, professional dental hygiene is the most effective, but recently a number of special abrasive toothpastes have been accepted by dental organizations as partially removing adhered plaque and the tartar which subsequently forms from the plaque.
2. Antimicrobial action could affect plaque formation in two ways, (a) reducing the number of bacteria in the mouth which form the mucopolysaccharides and (b) killing those bacteria trapped in the film to prevent further growth and metabolism.
3. Removal of plaque precursors requires the reduction of food sources and building blocks required for the bacteria to synthesize the mucopolysaccharides which polymerize into the plaque film. Going far back into the chain of events leading to plaque formation and interrupting the chain has much to commend it as a sound oral hygiene strategy. However, for this strategy to be effective, the plaque building blocks must be interrupted periodically. As noted above, heretofore, the oral hygiene preparations described above fall short on "frequency-of-use" basis.
For reference see: L. Menaker, The Biologic Basis of Dental Caries, Chapters 5, 11, 12, 14, 16 and 18, Harper & Row (1980). See also U.S. Pat. Nos. 4,465,661; 3,507,955; 4,902,497; 4,661,341; 4,666,708; 4,537,778; 4,657,758; 3,624,120; 4,525,342; 4,476,107; 5,078,988; 2,806,814; 4,774,077; 4,612,191; 4,353,890; 4,894,220; British Pat. No. 689,679, Gatter et al., Journal of Pharmaceutical Sciences, 74: 1228-1232 (1985); and Bass, Dent. Items of Interest, 70: 921-34 (1948).
As to Anti-Gingivitis Benefits:
It is generally accepted that antimicrobial substances are most effective in responding to gingivitis flare ups/infections of the gums. Suitable antimicrobials include stannous fluoride, as described in: U.S. Pat. Nos. 5,057,308; 5,057,309; 5,057,310 and in the FDA filing responsive to the Sep. 19, 1990 call-for-data (55 Fed. Reg. 38560) filed by WhiteHill Oral Technologies Jun. 17, 1991, Docket 81N-0033, OTC 210246 to 210262 and 210339 and specifically the "Annotated Bibliography set out in Vol. VI of said filing.
Other anti-gingivitis antimicrobials include chlorhexidine, halogenated diphenyl ethers such as triclosan, phenol and its homologs and the essential oils used in Listerine.RTM.. U.S. Pat. Nos. 4,022,880 and 4,894,220 disclose and claim various triclosan based oral care products. U.S. Pat. No. 4,894,220 includes an extensive teaching on phenol and its homologs suitable as antimicrobial agents. Metronidazole is discussed in detail in U.S. Pat. No. 4,568,535. The Listerine.RTM. essential oils are described in detail by Kornman in Journal of Periodontal Research, Supplement 1986: 5-22 (1986).
Other anti-plaque active ingredients include:
a. Quaternary ammonium compounds including benzethonium chloride, cetylpyridinium chloride as described by Volpe et al., Journal of Dental Research, 48: 832-841 (1969) and Gjermo et al., Journal of Periodontal Research, 5: 102-109 (1970).
b. Phenolic compounds including the mixture of thymol, eucalyptol, menthol along with methyl salicylate described as "essentials oils" in Listerine.RTM.. See Fornell et al., Scandinavian Journal of Dental Research, 83: 18-25 (1975), Lusk et al., Journal of the American Society of Preventive Dentistry, 4: 31-37 (1974); Gomer et al., Journal of the American Society of Preventive Dentistry, 2: 12-14 (1972).
As to Periodontitis Benefits:
The main cause of tooth loss in adults is periodontal disease. Yet, surprisingly, less than one percent of the public expenditures for dental treatment is for periodontal disease (see J. Dent. Educ., 43: 320 (1979). This is because conventional periodontal treatment is too expensive for most individuals, mainly due to the labor intensive, symptomatic treatment that is usually performed by highly skilled specialists.
Periodontal disease is an all-inclusive term for a variety of clinical entities that are forms of either gingivitis or periodontitis. Gingivitis is an inflammation of the gingiva or gums that can be associated with poor oral hygiene and/or hormonal states of the host. It is assumed, but not proven in the human, that gingivitis will progress to periodontitis, which is the form of the disease in which the infection has progressed to involve the oral tissues which retain the teeth in the jaw bone. Periodontitis is the more severe form of the disease, and if untreated, will eventuate in the loss of the tooth.
Dentists have long assumed that periodontal disease originates by the overgrowth of bacteria on the tooth surfaces in aggregates known as dental plaque. If this plaque persists for long periods of time on the tooth surfaces, it may in some instances calcify, forming the hard substance known as calculus. Numerous studies describe chemical agents which can in vitro and in vivo reduce plaque formation and calculus. However, none of these chemical agents has been reported to be successful in treating periodontitis.
A substantial number of different types of compounds and compositions have been developed for use as antibacterial and antiplaque agents, e.g., benzethonium chloride and cetyl pyridinium chloride, disclosed in U.S. Pat. No. 4,110,429, or as anticalculus agents, e.g., 2-phosphono-butane 1,2,4-tricarboxylic acid, disclosed in U.S. Pat. No. 4,224,308. These compounds are designed to be used by the individual in dentifrices, dental powders, pastes, mouthwashes, nonabrasive gels, chewing gums, topical solutions and the like, e.g., see U.S. Pat. No. 4,205,061. They are designed to be used as prophylactic agents, usually without requiring a prescription or supervision during usage, e.g., see U.S. Pat. No. 4,251,507. Often they are compounded with detergents and other cleaning agents, and this cleaning action is often an important aspect of the invention, e.g., see U.S. Pat. Nos. 4,251,507 and 4,205,061.
Recent research in periodontal disease (see, for example, Chemotherapy of Dental Plaque Infections, Oral Sci. Rev., 9: 65-107 (1976) indicates that gingivitis and periodontitis are characterized by different types of bacteria. Gingivitis is associated with the accumulation of Gram positive cocci and actinomyces, whereas periodontitis is characterized by proportional increases in anaerobic bacteria, such as spirochetes and black pigmented bacteroides (see "Host-Parasite Interactions in Periodontal Disease," R. J. Genco and S. E. Mergenhagen, eds. Amer. Soc. for Microbiol. Washington, D.C. p. 27-45, 62-75, 1982). The different bacterial compositions of plaque associated with either gingivitis or periodontitis suggest that a mode of treatment that is effective in gingivitis may not be effective in periodontitis. Previous discoveries in the area of periodontal disease have assumed that there is no bacterial specificity in periodontal disease. This is now known to be incorrect. These bacterial differences in plaque may explain why an agent effective in plaque control, such as chlorhexidine, has little effect on gingivitis and no published effect on periodontitis.
Another important finding from recent periodontal research is that the composition of the dental plaque will differ according to its location on the tooth surface. Above the gingival or gum margin, facultative bacteria, such as Gram positive cocci and rods, are numerically dominant, whereas below the gum margin, anaerobic motile bacteria such as spirochetes, and anaerobic Gram negative rods including the black-pigmented bacteroides are predominant. In other words, two different microbial ecosystems are present on the same tooth surface.
Periodontal disease is a condition caused by a pathogenic microbial ecology established within the gingival sulcus which deepens to become a periodontal pocket. This microbial ecology, located deep within the periodontal pocket, differs greatly from that of the superficial oral environment by being more anaerobic, having a larger number of Gram negative organisms, and having a greater proportion of motile species.
Several factors impede the diffusion of medicinal agents when applied to the superficial periodontal tissues. Anatomically, the gum tissue is closely adapted to the neck of the teeth, mechanically restricting the diffusional pathway. In addition, a fluid termed gingival crevice fluid, with the approximate composition of plasma, permeates the periodontal environment and is continually produced by the diseased periodontal tissues at a rate of 10 to 100 microliters per hour. This fluid, emanating from the diseased pocket lining, creates a net outward flow further impeding the introduction of medications from superficially applied drug delivery devices. These interferences are sufficiently effective to insulate the pocket environment to the extent that saliva does not penetrate, and topically applied medicinal agents such as rinses have been found largely ineffectual in the treatment of established periodontitis, because of their relatively short "residual" time on mouth surfaces.
Although mouth rinses may be effective in the reduction of gingivitis resulting from poor home care procedures, heretofore the effective radius of action of these agents does not extend to the periodontal pocket. Traditionally, introduction of antibacterial agents in solution form into the periodontal pocket is similarly ineffective due to the rapid clearance of such agents so that the duration of contact at the active site has been minimal.
Conventional therapy for periodontal disease, as first enunciated by Pierre Fauchard in 1746 in his book entitled "The Surgeon Dentist, a Treatise on Teeth," involves the mechanical removal of bacterial plaques and accumulations from the periodontal pocket at periodic intervals. This may include periodontal surgery to achieve access and to recontour damaged tissues. These procedures require a high degree of technical expertise from the practitioners of the art, are expensive, and often result in pain, extensive bleeding, and general discomfort on the part of the patient so treated. Since these procedures provide, at best, only temporary reduction in bacterial populations, they must be repeated at regular intervals to be effective. As discussed by Lindhe and coworkers in "Healing Following Surgical/Non-Surgical Treatment of Periodontal Disease" in the Journal of Clinical Periodontology, Vol. 9, pages 115-128, the frequency of repetition needed for optimal results may be as high as once every two weeks.
Methods for administering drugs for periodontal therapy have heretofore largely been concerned with superficial application. For example, long-acting capsules or tablets held in the mouth (see U.S. Pat. No. 3,911,099); buccal implants for releasing drugs into the saliva (see U.S. Pat. No. 4,020,558); topically applied gels (see U.S. Pat. No. 3,679,360); topically applied drug-containing bandages (see U.S. Pat. No. 3,339,546); a drug-containing plastic hardenable mass (see U.S. Pat. No. 3,964,164); a medicated periodontal dressing (see U.S. Pat. No. 3,219,527); a topical dressing composed of a finely divided particulate carrier and suspended medicinal agents (see U.S. Pat. No. 3,698,392); a bandage for covering moist mucosal surfaces (see U.S. Pat. No. 3,339,546); a microencapsulated liquid droplet formation for topical application to the gums of dogs and other animals (see U.S. Pat. No. 4,329,333); and foam-film devices containing medication (see U.S. Pat. No. 3,844,286). In addition, several fibrous forms for superficial medication have been described, including impregnated or drug-releasing forms of dental floss (see U.S. Pat. Nos. 3,417, 179, 2,667,443, 2,748,781, and 3,942,539); solid absorbable fibers of polyglycolic acid with medicants incorporated therein (see U.S. Pat. No. 3,991,766); and cellulose acetate hollow fibers (see U.S. Pat. No. 4,175,326). See also U.S. Pat. No. 4,892,736.
It has been reported in deliberations before a Food and Drug Administration (FDA) Panel evaluating plaque and gingivitis claiming ingredients (see 55 Fed. Reg. 38560) that ethanol at 36.9% is required to solubilize the combination of lipophilic antimicrobial actives: eucalyptol at 0.9%, thymol at 0.63%, methyl salicylate at 0.55% and menthol at 0.055%; in order to transport these activities into the dental plaque biofilm within the recommended 30 second rinse period.
Specifically, in vitro biofilm studies have established that Listerine's alcohol diffuses from a region of higher concentration into the dental plaque biofilm, transporting the lipophilic antimicrobial essential oils. These Listerine.RTM. transport kinetics (See FIG. 8) allow Listerine.RTM. to achieve the impressive antiplaque and antigingivitis clinical effects as reported for this rinse in the literature.
The FDA is presently deliberating the safety of high level ethanol containing mouth rinses, i.e., above 25% ethanol. The need for comparable antiplaque and antigingivitis rinses containing the essential oil actives at lower alcohol levels is particularly critical in view of the extensive "safety" deliberations underway at the FDA for high level ethanol rinses.
All of the foregoing references and the references cited in these references are incorporated in the description of the present invention.